Download Neuronal Activity in Substantia Nigra Pars Reticulata during Target

The Journal of Neuroscience, March 1, 2002, 22(5):1883–1894
Neuronal Activity in Substantia Nigra Pars Reticulata during Target
Selection
Michele A. Basso1 and Robert H. Wurtz2
Department of Physiology, University of Wisconsin–Madison, Madison, Wisconsin 53706, and 2Laboratory of
Sensorimotor Research, National Eye Institute, Bethesda, Maryland 20892
1
Complex visual scenes require that a target for an impending
saccadic eye movement be selected from a number of possible
targets. We investigated whether changing the number of stimuli from which a target would be identified altered the activity of
substantia nigra pars reticulata (SNr) neurons of the basal
ganglia (BG) and how such changes might contribute to
changes we observed previously in the superior colliculus (SC).
One, two, four, or eight visual stimuli appeared on random trials
while monkeys fixated a centrally located spot. After a delay,
one of the stimuli in the array changed luminance, indicating
that it was the saccade target. We found that SNr neurons that
had a pause in tonic activity after target onset and when the
saccade was made to the target showed a modulation of
activity during the multitarget task. Because the number of
stimuli in the array increased from one to eight, the initial pause
after the onset of the visual stimulus decreased. Activity during
the preselection delay was reduced but was independent of the
number of possible targets present. When one of the stimuli
was identified as the saccade target, but before the saccade
was made, we found a sharp decline in activity. This decline
was related to the monkey’s selecting the target rather than the
luminance change identifying the target, because on error trials,
when the luminance changed but a saccade was not made to
the target, the activity did not decline. The decline for the
preferred target location was also accompanied by a lesser
decline for adjacent locations. Our findings indicate that SNr
activity changes with target selection as it does with saccade
initiation and that the SNr could make substantial, direct contributions to the SC at both times. The pause in SNr activity with
target selection is consistent with the hypothesis that BG provide a disinhibition for the selection of desired movements.
Visual scenes encountered during natural viewing require that a
single stimulus be selected out of many possible to serve as an
object directing visual attention or as a target identifying a goal for
actions. Voluntary saccadic eye movements, those rapid reorienting
movements of the eye, are an elegant model behavior in which to
study target selection for action, because goal directed movements,
by definition, require the identification of a single goal.
Our previous work examined the role of intermediate layer
superior colliculus (SC) neurons in a task in which one target of
many possible was identified for a saccadic eye movement. We
found that the activity of SC neurons reflected the probability
that a particular saccade target would be selected for a saccade
(Basso and Wurtz, 1998). Similar reports have been described for
these neurons in gap saccade tasks (Dorris and Munoz, 1998).
Therefore, some SC neuronal activity is not obligately linked to
the production of a saccade and therefore may reflect processes
intervening between vision and action (Glimcher and Sparks,
1992; Munoz and Wurtz, 1995).
Because the basal ganglia (BG) receive direct input from
multiple cortical regions reflecting target selection as well as areas
modulated by visual attention (Selemon and Goldman-Rakic,
1985, 1988; Boussaoud et al., 1992; Parthasarathy et al., 1992), and
the substantia nigra pars reticulata (SNr), one of two output
nuclei of the BG, has direct projections to the SC (Hopkins and
Niessen, 1976; Anderson and Yoshida, 1977; Deniau et al., 1978;
Graybiel, 1978; Beckstead, 1983; Hikosaka and Wurtz, 1983d;
Karabelas and Moschovakis, 1985), in the current experiment we
hypothesized that we would see activity modulation in the SNr
reflecting changes in target probability. Changes in SNr activity
might occur under the same conditions as those seen in SC and
therefore might be regarded as precursors to the SC changes that
were related to target selection.
Recent experimental work has inspired a renewed consideration of the role of BG nuclei in events other than movement
initiation. For example, anatomical (Hazrati and Parent, 1992a,b;
Parent and Hazrati, 1993) and physiological data (Mink and
Thatch, 1991a,b) suggest that BG are involved in selecting preferred movements through disinhibition and suppressing activity
associated with nonpreferred movements through inhibitory
mechanisms (Mink and Thatch, 1993; Mink, 1996). Indeed, that
SNr neurons pause for saccadic eye movements is strong support
for the role of disinhibition from the BG in movement initiation
(Hikosaka and Wurtz, 1983a,c,d; Handel and Glimcher, 1999,
2000). We reasoned that we could address some of the issues
related to events before saccade initiation in the SNr, as we had
done previously in the SC. Therefore, in the present work, we
recorded SNr neurons while subjects performed the same behavioral task that we used previously to measure SC neuronal
activity.
Received Oct. 9, 2001; revised Dec. 17, 2001; accepted Dec. 18, 2001.
We are grateful to Dr. John McClurkin for data analysis software, the Laboratory
of Diagnostic Radiology at National Institutes of Health for providing magnetic
resonance images, Dr. Harvey Karten and Agnieska Brzozska-Precthl for immunohistochemical processing of the tissue, and Jennifer Pokorny for her assistance
during the preparation of this manuscript.
Correspondence should be addressed to Dr. Michele A. Basso, Department of
Physiology, University of Wisconsin, Madison, Medical School, 1300 University
Avenue, Room 291 MSC, Madison, WI 53706. E-mail: michele@physiology.
wisc.edu.
Copyright © 2002 Society for Neuroscience 0270-6474/02/221883-12$15.00/0
Key words: saccade; primate; inhibition; disinhibition; competition; vision
1884 J. Neurosci., March 1, 2002, 22(5):1883–1894
Three observations from our previous work (Basso and Wurtz,
1998) are relevant to the present experiment. First, as the number
of possible targets increases, the activity of SC neurons decreases,
which is evidence of lateral interactions. Second, when a single
target is identified out of the many possible, the activity of SC
neurons increases to levels seen when only a single target is
present, overcoming the inhibitory interactions and analogous to
changes seen in cortical regions when visual attention is directed
to the preferred target. Third, when monkeys make saccades to
targets located adjacent to and opposite the preferred response
field, the activity of some SC neurons is suppressed. This finding
is similar to that seen in the frontal eye field (Schall and Hanes,
1993; Schall, 1995; Schall et al., 1995) and may reflect a mechanism of target selection for saccades.
By examining the activity of SNr neurons as we did with SC and
comparing the results with those that we obtained previously in
the SC, we could determine whether SNr activity modulations
could be directly responsible for the expression of SC activity
modulations. We found that SNr neurons were modulated by
changes in the probability that a particular stimulus would become the target for the saccade, consistent with a role for these
neurons in target selection for saccades. However, given the
nature of the modulations in SNr seen with changes in target
probability, additional modulations must be responsible for the
modulation of SC with changes in target probability. In sum, the
SNr activity changes are consistent with, and provide constraints
on, recent views of BG function and behavioral selection.
MATERIALS AND METHODS
Physiolog ical procedures. T wo monkeys were prepared for chronic electrophysiological recording of single neurons and eye movements. Anesthesia was induced initially with an intramuscular injection of ketamine
(10.0 mg / kg), valium (1.0 mg / kg), and glycopyrrolate (0.01 mg / kg).
Monkeys were intubated and maintained at a general anesthetic level
with isofluorane. A subconjunctival eye coil was implanted (Judge et al.,
1980). A plastic head holder for restraint and a cylinder for microelectrode recording were mounted on the top of the exposed skull and
secured with titanium screws and dental acrylic. This hardware allowed
subsequent magnetic resonance images to be obtained. For access to the
SC, the recording chamber was placed stereotaxically on the midline and
angled 38° back so that the electrode penetrations were directed caudorostral, toward the SC. For the SNr, two cylinders were placed on the
skull. The cylinder on the left side was angled 30° lateral –medial at
stereotaxic coordinates, anteroposterior (AP) 9.0 and mediolateral (ML)
⫺5.0 (O. Hikosaka, personal communication). The second cylinder was
placed on the right side at stereotaxic coordinates AP 9.0 and ML 5.0,
parallel to the surface of the skull, i.e., a 0° angle. This approach allowed
straight vertical penetrations through the ventrobasal complex of the
thalamus (V PM) and provided recording of the trigeminal recipient
neurons of the thalamus as a landmark (A. Handel, P. Glimcher, and W.
Schultz, personal communication). Figure 2 shows coronal sections
through the SNr of one of these monkeys with a 0° penetration. At the
end of surgery and 1 d after the operation, animals were given Banamine
for analgesia. An antibiotic (Polyflex) was given 1 d before the operation
and every other day for 14 d after the operation. Monkeys recovered for
1 week before behavioral and physiological recording commenced. All
protocols were approved by the Institute Animal C are and Use Committee and complied with the Public Health Service Policy on the
humane care and use of laboratory animals.
Single neurons were recorded with tungsten microelectrodes (Frederick Haer) with impedances between 0.7 and 1.5 M⍀ measured at 1 kHz.
Electrodes were aimed toward the recording site through stainless steel
guide tubes held in place by a delrin grid that was secured to the
recording chamber (Crist et al., 1988). Action potential waveforms from
individual neurons were identified with a window discriminator that
returned a transistor–transistor logic (TTL) pulse for each waveform that
met both time and amplitude criteria. The time of occurrence of each
action potential was stored with 1 msec resolution. To identif y the SNr
before the experiment, we searched for neurons that were antidromically
Basso and Wurtz • Basal Ganglia and Selection
activated by stimulation within the SC (Hikosaka and Wurtz, 1983d). For
this, electric current was passed through tungsten microelectrodes (Frederick Haer) with impedances between 0.1 and 0.7 M⍀ measured at 1
kHz. Single, biphasic pulses 150 ␮sec in duration were used. Current
intensities varied with the searching currents ranging between 200 and
1000 ␮A. Antidromic currents varied between 50 and 400 ␮A (Lemon,
1984). Neurons identified as antidromic had a short (⬍2.0 msec) and
consistent latency and were also subjected to the collision test (Fuller and
Schlag, 1976). For this, the TTL pulse derived from a spontaneously
occurring SNr spike was provided as input to a stimulator (Astro-Med
Instruments S88) providing a current-balanced pulse to the SC. This test
was inconclusive in some cases because of the short latency of the SNr
antidromic spike and the delays inherent in the hardware used for the
production of the TTL pulse (W EXv3.0a) (Chandra and Optican, 1997).
At least one of both classes of neuron described in this report could be
driven antidromically. The number of antidromic neurons was not large
enough (n ⫽ 9) to draw conclusions about the projection pattern to the
SC. Our purpose for using the antidromic technique was to confirm that
our recordings were within the SNr.
Behavioral procedures. All behavioral paradigms and storage of data
were controlled by a 486PC running a QN X-based real-time data acquisition system (REX) (Hays et al., 1982). During experiments, monkeys
were seated in an adjustable primate chair facing a screen with their
heads restrained for the duration of the experiment (3–5 hr). The visual
display on the screen was rear projected by a television projector (Liquid
Crystal, Sharp) operating at 60 Hz. The tangent screen was located 57 cm
in front of the monkeys. The centrally located fixation point was a
projected image of a light-emitting diode (L ED). Eye movements were
recorded with the magnetic search coil technique (Fuchs and Robinson,
1966), and horizontal and vertical eye position signals were sampled at 1
kHz. An interactive computer program was used to make measurements
and calculate metrics and dynamics of eye movements (DEX). Saccades
were detected using velocity (10 –25°/sec) and acceleration (500 – 800°/
sec 2) criteria, and the data were inspected by the experimenter for
corrections.
Neurons were identified while monkeys performed visually guided
saccades or delayed saccades either memory guided (Hikosaka and
Wurtz, 1983c) or visually guided. In the former task, a centrally located
fixation point appeared, and the monkeys were required to maintain
fixation of this spot within an electronic window of 2°. A peripherally
located spot was presented for 200 msec while the monkeys maintained
fixation. After a delay of 200 – 800 msec in which selection could occur,
the fixation point was removed, and monkeys made a saccade to the
location of the previously flashed target spot. In the later task, the target
spot remained illuminated throughout the trial. For visually guided
saccades, the fixation spot disappeared at the same time the target spot
appeared, i.e., 0 msec delay. We determined the general characteristics of
the neuronal activity and an estimate of the center of the preferred field
by requiring monkeys to make saccades to different locations in the visual
field. In general the fields of SNr neurons were large, in some cases
encompassing an entire hemifield (Handel and Glimcher, 1999). We did
not attempt to characterize the field f ully. We made a qualitative assessment on-line about the preferred location on the basis of the largest
decline in activity. During all experiments, monkeys were rewarded with
a drop of fruit juice or water. Monkeys worked daily until satiated and
were given supplemental fluid as required. The monkeys’ weight was
monitored daily, and they remained under the supervision of the institute
veterinarian.
Target probabilit y task. To determine the effect of target probability on
SNr neuronal activity, we used the same multitarget task that we used
previously for recordings in the SC (Basso and Wurtz, 1998). The details
of this task are described below.
In the multitarget task (Fig. 1), our goal was to separate the sequence
of events leading up to saccade generation while varying the probability
that a given stimulus would become a saccade target. First, a centrally
located fixation point (L ED) was illuminated, and monkeys were required to look at it for 1 sec to initiate the trial. Second, one, two, four,
or eight spots of light were projected for a randomized time ranging from
800 to 1200 msec, and these trial types were randomly interleaved. This
was the period of preselection because the monkeys did not know which
of the spots would become the target. One of these possible targets was
always located at the position in the visual field that yielded the maximal
response of SNr neurons, in this case a maximal pause in activity. All
other possible targets were placed equally eccentric but in different
directions (in the four cardinal and four oblique directions, 45° between
Basso and Wurtz • Basal Ganglia and Selection
J. Neurosci., March 1, 2002, 22(5):1883–1894 1885
Figure 2. The SNr and SNc of a rhesus monkey. Two adjacent (50 ␮m)
coronal sections are presented. In A, the section was stained with cresyl
violet and the electrode path is evident (arrow). In B, the adjacent section
was stained immunohistochemically for tyrosine hydroxylase (TH ), the
rate-limiting enzyme in the synthesis of the neurotransmitter dopamine
(Cooper et al., 1986). The brown reaction product indicates the presence
of TH. These sections demonstrate that the electrode penetrations made
in these experiments passed through the SNc and into the SNr. CP,
Cerebral peduncle; LGN, lateral geniculate nucleus.
Figure 1. Multitarget task. Along the top, the bars labeled fixation, array
on, and target dim depict the temporal sequence of the behavioral task
used in this experiment. The line below, labeled Eye, is a schematic of eye
position. The bottom portion of the figure depicts the spatial arrangement
of the task and the different trial types. The large boxes are the screen on
which visual stimuli were displayed. The cross represents the fixation
point, and the small box indicates the eye position criterion window for
correct performance of the task. Each of these trial types was randomly
interleaved. As the number of possible target increased, the probability
that any one would be identified for a saccade was decreased. The fixation
period began with the onset of a fixation point located centrally on the
screen. This was followed by a preselection period when the array of
possible targets appeared. The selection period is indicated by the time in
which the saccade target was identified by a reduction in luminance. The
initiation period commenced when the cue to make a saccade, the removal
of the fixation point, occurred. Each period of the task was separated by
a random interval.
each of eight stimuli). The eccentricities ranged from 5 to 25°, with most
being between 10 and 15°. Third, one of the possible targets dimmed for
800 –1200 msec. We defined this as the period of selection because the
dimming indicated which of the spots was the target for the saccade. The
final period of saccade initiation began when the fixation point went off
(go signal), which required the monkeys to make a saccade within 500
msec to the dimmed target. Monkeys were required to maintain their eye
position at the target for 300 –500 msec to obtain liquid reward. The data
that we present are taken from trials in which the monkeys performed the
task correctly and made saccades to the target located within the center
of the preferred field, unless stated otherwise. The task had a clear target
change so that it was essentially a pop-out task (Bravo and Nakayama,
1992) requiring only target detection, not discrimination (Treisman and
Gelade, 1980).
Data anal ysis. In addition to descriptive statistics, we used parametric
statistical procedures, provided the initial tests of normality were successf ul. When we compared more than two levels of a variable, we used
the ANOVA. When we compared only two levels of a variable, we used
t tests. For multiple group comparisons, such as those in the multitarget
task, we used repeated measures ANOVA with the T ukey test method
for post hoc pairwise comparisons. If normality tests failed, the nonparametric equivalent of these tests was used. Comparisons generally involved measuring the mean level of discharge for the neurons in the one,
two, four, and eight possible target conditions. We did this separately for
successive time intervals in the task. For example, to analyze the visual
response of neurons in the task, we performed a one-way ANOVA with
four levels, namely, one possible target condition, two possible targets
condition, four possible targets condition, and eight possible targets
condition. When a main effect was obtained, we performed the pairwise
comparisons using the T ukey test to determine which pair contributed to
the significant difference.
RESULTS
Neuronal classes
We recorded from 81 neurons in two monkeys in four hemispheres. Of the 81 neurons, 58 had activity related to visual
stimuli or saccades or both and will be the focus of the present
report. In addition to using antidromic activation (Materials and
Methods), we identified the SNr (Fig. 2) by observing the activity
profiles of the neurons while monkeys performed the visually
guided saccade task and the delayed saccade task (either visually
guided or memory guided). We classified the neurons according
to their activity in three periods during performance of a delayed
saccade task to the preferred target location (or in the single
target condition of our multitarget task if no delayed saccade task
was performed): baseline period, 200 msec before visual stimulus
onset while the subject actively fixated; visual period, 100 –300
msec after visual stimulus onset; and saccade period, 150 msec
before and after saccade onset. We identified two types of SNr
neurons (Fig. 3). “Visual-saccade” neurons had a decline of at
least 1 SD below baseline during either the visual or both the
visual and the saccade intervals for a least 15% of the trials (n ⫽
38). “Saccade” neurons had a decline in activity for at least 1 SD
below baseline for at least 15% of the trials only during the
saccade interval (n ⫽ 20).
For the other 23 of the 81 neurons, 2 were recorded from the
zona incerta as indicated by their tonic firing rate and their
omnidirectional pause in activity associated with the onset of
1886 J. Neurosci., March 1, 2002, 22(5):1883–1894
Figure 3. Examples of neuronal activity profiles in the SNr. The left
column is aligned on the onset of the visual target (vertical dashed line and
arrow), and the right column is aligned on the saccade (vertical dashed line
and arrow). Eye position traces are plotted, superimposed as a function of
time. Individual ticks are action potentials, and each row of ticks is a trial.
Spike density functions are superimposed on the raster diagram. The spike
density functions were calculated with a Gaussian of 12 msec. A, SNr
visual-saccade neurons have a pause for the onset of the visual stimulus as
well as before the saccade. B, SNr saccade neurons show a decline in
activity at the time of the saccade.
visually guided saccades (Ma, 1996) and spontaneous saccades
(Hikosaka and Wurtz, 1983a). Thirteen neurons recorded were
not related to saccades or to visual stimuli and were not modulated in our task. Eight neurons showed pauses in activity with the
onset of the fixation point as described by Hikosaka and Wurtz
(1983b). In our task, these neurons reduced their activity at the
time of fixation and remained at that level throughout the duration of the trials independent of the number of stimuli. These 23
neurons will not be considered further.
Multiple stimulus interactions
Visual-saccade neurons
The 38 SNr visual-saccade neurons had tonic spontaneous activity that showed systematic decreases throughout the trial in the
multitarget task, and these sequential changes are best illustrated
in the one target condition of this task (Fig. 4, One). After the
stimulus appeared, the activity decreased (Fig. 4, One, left column). This decreased activity recovered to a tonic level later in
the preselection delay period, but this level was less than the
spontaneous level (Fig. 4, One, left column). At the time the target
dimmed at the beginning of the selection delay period, the neuronal activity declined precipitously (Fig. 4, One, middle column,
vertical dashed line). This decline in activity was maintained until
Basso and Wurtz • Basal Ganglia and Selection
Figure 4. Effect of changes in target probability on an SNr visual-saccade
neuron. The events of the task are indicated as the labeled periods across
the top. The eye position trace is a schematic. The first row of rasters is for
correct responses in the single possible target condition (One), the second
is when two possible targets appeared (Two), and the third is when four
possible targets appeared (Four). The last row is when eight possible
targets appeared (Eight). The columns of rasters are aligned on the events
of the task: the first is aligned on when the stimuli appear, the second is
aligned on target identification, by dimming, and the last is aligned on
saccade initiation. Each tick in the raster is a single action potential, and
each row of ticks is an individual trial. The lines superimposed are spike
density functions (␴ ⫽ 12 msec). All data are taken from correct trials
when the target was identified in the preferred field of the recorded
neuron. The arrowheads and the vertical dashed lines indicate the trace
alignment. The initial pause decreased with increasing numbers of possible targets, and at the time the target was identified (middle column,
vertical dashed line), the activity dropped precipitously. Vertical calibration bar: 100 spikes/sec.
the saccade was initiated, showed a further dip with the saccade,
and then eventually returned to baseline tonic levels shortly
thereafter (Fig. 4, One, right column). Use of the multitarget task
shows that in addition to the well established decreases in activity
related to visual target onset and saccade initiation, these SNr
neurons showed both a tonic depression of activity in the preselection period and a sharp decline in activity when the instruction
to make the saccade was given at the start of the selection period.
As the number of possible targets increased, the pause associated with the onset of the stimulus array decreased, and this
pause was absent in the presence of eight possible targets (Fig. 4,
Basso and Wurtz • Basal Ganglia and Selection
J. Neurosci., March 1, 2002, 22(5):1883–1894 1887
Figure 5. The activity across the sample of visualsaccade SNr neurons was modulated with changes in
target probability. The traces show the mean spike density function of 38 SNr neurons in each target probability
condition. For these traces, the target was always located
in the center of the response field, and the trials were
performed correctly. The black bars indicate a statistically significant difference between the four conditions
during the measurement intervals. The gray bars indicate
a lack of statistical significance. The initial preselection
measurement interval was from 100 to 400 msec after the
stimuli appeared. The second preselection interval was
400 msec before the target was identified. Because there
was a minimum of 800 msec between task events, there is
no overlap in the trace or the measurement intervals.
The selection interval was 100 –500 msec after the target
dimmed.
Figure 6. The activity across the sample of saccaderelated SNr neurons was not modulated with changes in
target probability. The traces show the mean spike density
function of 20 SNr neurons in each target probability
condition. The arrangement of this figure is identical to
that in Figure 5. For these traces, the target was always
located in the center of the response field, and the trials
were performed correctly. The gray bars indicate a lack of
statistical significance. The initial preselection measurement interval was from 100 to 400 msec after the stimuli
appeared. The second preselection interval was 400 msec
before the target was identified. Because there was a minimum of 800 msec between task events, there is no overlap
in the trace or the measurement intervals. The selection
interval was 100 –500 msec after the target dimmed. Note
that these neurons showed a clear decline in activity before the saccade was initiated. Vertical calibration: 20
spikes/sec.
Two, Four, Eight, left column). During the preselection delay
period, the decreased tonic level of activity did not differ as the
number of possible targets increased (Fig. 4, left side of middle
column in One, Two, Four, Eight). At the time the target was
identified, the decline in neuronal activity did not change as the
number of possible targets increased (Fig. 4, dashed line, middle
column). When the fixation point was removed, a saccade to the
target was cued, and there was a modest, additional decline in
activity at the time of the saccade. This saccade-related decline
also was the same regardless of the number of stimuli (Fig. 4,
vertical line, right column).
We averaged the neuronal activity from the sample of 38
visual-saccade neurons across the different periods of the task for
each possible target condition and superimposed the averaged
traces (Fig. 5). The pattern of activity across the sample was
similar to the example neuron shown in Figure 4. As the number
of possible targets increased, the pause in activity after the stimulus
onset decreased (Fig. 5, left plot). The difference in the initial visual
pause (50 –200 msec after stimulus onset) in the different possible
target conditions was statistically significant (ANOVA; F(3,151) ⫽
20.09; p ⬍ 0.001). Pairwise comparisons performed with the Tukey
test revealed that all conditions contributed to the overall signifi-
cance ( p ⬍ 0.03) except the difference between possible targets
conditions 1 and 2 ( p ⫽ 0.97).
During the remainder of the preselection period, the activity
was not significantly modulated with the number of possible
targets (ANOVA; F(3,303) ⫽ 0.18; p ⫽ 0.95), but the activity that
was measured 400 msec before the target dimmed remained
below the baseline level (200 msec before the array onset) across
all conditions when differences among individual neurons were
allowed (ANOVA; F(1,303) ⫽ 158.39; p ⫽ 0.001) (Fig. 5, middle
plot). At the time the selection period began, when the target
dimmed (Fig. 5, middle plot, selection) the activity of the neurons
declined dramatically, and the decline occurred similarly for each
condition (1, 2, 4, and 8). Comparison of the activity 400 msec
before the target dimmed and 400 msec after the target dimmed
for each possible target condition revealed significant differences
(ANOVA; F(1,303) ⫽ 7.31; p ⬍ 0.007). The amount of decline did
not differ between the numbers of possible targets as indicated
from the interaction term (ANOVA; F(3,303) ⫽ 0.13; p ⫽ 0.94)
(Fig. 5, middle plot, selection). At the time of and after saccade
onset (Fig. 6, vertical dashed line in last set of traces), there was an
additional decline in activity [see also Hikosaka and Wurtz
(1983a)].
Basso and Wurtz • Basal Ganglia and Selection
1888 J. Neurosci., March 1, 2002, 22(5):1883–1894
In summary, for the visual-saccade neurons, as the number of
possible targets increases, the pause associated with the onset of
the visual stimuli decreases. The activity in the preselection delay
period remains below baseline but is independent of the number
of possible targets. At the time the target becomes available for
selection, the neuronal activity drops sharply, regardless of the
number of visual stimuli present. The drop-off in activity remains
until well after the saccade onset, at which point the neuronal
activity returns to spontaneous levels.
Saccade neurons
The 20 saccade neurons had tonic, spontaneous activity that
decreased only around saccade onset. In our multitarget task, the
saccade neurons behaved differently from the visual-saccade neurons already described. In the single target condition, saccade
neurons maintained a tonic rate of activity that was not different
from the baseline level of firing and was maintained throughout
the trial until slightly before saccade onset (Fig. 6, thickest black
line). At the time of the saccade, there was a clear pause in
activity that lasted the duration of the saccade and increased back
to spontaneous levels at ⬃300 msec after the saccade (Fig. 6,
selection). As the number of possible targets increased, the activity of saccade neurons across the sample was modulated slightly.
With eight possible targets, the initial activity after stimulus onset
increased (Fig. 6, thinnest black line) and then rapidly decreased,
as if transiently oscillating. Nevertheless, the initial activity (50 –
200 msec after stimulus onset; shaded gray bar on abscissa) was
statistically indistinguishable across the four possible target conditions (ANOVA; F(3,79) ⫽ 0.043; p ⫽ 0.988). To determine
whether there were some differences obscured by the large window, we divided the initial response into three smaller windows:
75–125 msec after stimulus onset, 125–200 msec after stimulus
onset, and 200 –300 msec after stimulus onset. We performed
ANOVAs on averaged spike counts during these intervals as well
as on spike counts normalized to the baseline activity (200 msec
before stimulus onset). The normalization was done individually
for each neuron. In the first window the average activity in the
single target condition was 79.57 spikes/sec, whereas with eight
possible targets the average activity was 82.57 spikes/sec. The
same trend was observed in the second window (84.26 vs 88.74
spikes/sec). In the third window, the opposite trend was revealed:
84 spikes/sec was the average rate for a single target, whereas
70.73 spikes/sec was the average rate with eight stimuli present.
Statistical analyses revealed that none of these differences were
statistically significant (ANOVA, F(3,79) ⫽ 0.073, p ⫽ 0.97, 75–125
msec window; ANOVA, F(3,79) ⫽ 0.102, p ⫽ 0.96, 125–200 msec
window; ANOVA, F(3,79) ⫽ 2.48, p ⬍ 0.07, 200 –300 msec
window).
Comparison of the preselection period (400 msec before the
target dimmed) to the period after a target was identified (400
msec after the target dimmed) revealed that the activity of saccade neurons did not change in any of the possible target conditions (ANOVA; F(1,159) ⫽ 0.459; p ⫽ 0.499). Additionally, there
were no differences in saccade activity during the selection period
for the different possible target conditions (ANOVA; F(3,159) ⫽
0.052; p ⫽ 0.985). Before the onset of the saccade, these neurons
showed a pause in activity that lasted the duration of the saccade
(Fig. 6, right plot). This pause did not differ for the different
numbers of possible targets.
Thus, saccade-related neurons of the SNr are not consistently
modulated with changes in the number of possible targets avail-
Figure 7. The activity decline of visual-saccade SNr neurons associated
with target identification predicts the impending saccade. The temporal
arrangement is shown on the top by the labeled bars. The vertical dashed
lines indicate the alignment of the traces. The top raster and spike density
functions are taken from trials in which four possible targets were presented and the monkey made an erroneous saccade to one of the other
stimuli. The bottoms rasters and spike densities are taken from correct trials
in the same four possible target conditions. Note that the time of saccade
initiation is not indicated for clarity. The decline in SNr neurons associated with the dimming of one stimulus to indicate it as the target for a
saccade does not occur if the monkey does not select the target as a goal
for a saccade.
able for saccades or at the time the target became available for
selection.
Error trials
Up to this point, we have considered only trials in which animals
performed the task correctly; that is, saccades were made to the
target that was identified during the selection period, and the
saccades were made in a timely manner (within 500 msec) and
were accurate within 2–3°. In some rare cases, however, monkeys
made saccades to the wrong target or failed to make a saccade at
all. This occurred infrequently because the task is simple and the
monkeys were well trained, but their occurrence provided an
opportunity to determine whether the change in SNr activity was
related to the target presented or to the monkey’s response to the
target. Figure 7 shows the trials for a single visual-saccade neuron
during trials with four possible targets. In some trials the monkey
performed the task correctly (Fig. 7, bottom plot, correct trials),
and in other trials the monkey made errors by making a saccade
to another location (Fig. 7, top plot, error trials). Initially the
neuron showed a pause associated with the onset of the visual
stimulus array regardless of the trial outcome (Fig. 7, left plot). In
correct trials, at the time the target dimmed, the activity of the
Basso and Wurtz • Basal Ganglia and Selection
J. Neurosci., March 1, 2002, 22(5):1883–1894 1889
neuron declined and remained low (Fig. 7, right plot). In contrast,
in the error trials, the neuronal activity did not decline or did so
slightly but returned quickly to its tonic level. This comparison
indicated that the pause in SNr neurons occurring after the
identification of the target but in advance of the saccadic eye
movement predicts the intent of the monkey rather than being
exclusively related to the stimulus change.
We confirmed this observation by examining all the error trials
across all the data. We found 79 error trials (18 neurons) in which
the monkey made a saccade to the wrong target or did not make
a saccade at all. We measured the average activity in a 400 msec
interval beginning 200 msec after the target dimmed in both
correct and errors trials for these neurons. The median activity in
errors trials was 79.61 spikes/sec, whereas the median activity in
correct trials was 46.25 spikes/sec. This difference was statistically
reliable as determined by a Wilcoxon signed rank test ( p ⬍ 0.01).
Thus, the pause in SNr neurons reflects the saccade target ultimately chosen by the monkeys rather than the visual stimulus on
the retina.
Spatial resolution of stimulus interactions
Contralateral and ipsilateral targets
A comparison of the neuronal activity during the conditions when
targets are presented in the preferred field of the neuron and the
field opposite allows an inference about the activity of neurons
coding nonpreferred target locations, similar to inferences made
in cortical neurons (Britten et al., 1992; Thompson et al., 1996), as
well as those made by us in our previous work in the SC (Basso
and Wurtz, 1998). Therefore, we compared the activity in the two
and eight possible targets conditions when the target in the preferred location was identified and when the target in the opposite
hemifield was identified. We averaged the activity of the sample of
visual-saccade neurons across the intervals of the task and superimposed the traces for the ipsilateral and contralateral target locations for the two possible targets condition (Fig. 8 A) and for the
eight possible targets condition (Fig. 8 B). For this comparison we
used the data from correct trials from visual-saccade neurons.
For both the two stimulus and eight stimulus trials, the first
difference between the activity of the SNr neurons with an ipsilateral target and a contralateral target occurred at the time the
target was indicated (Fig. 8, middle plot, vertical dashed line).
When the target was in the ipsilateral hemifield, there was no
decline in the neuronal activity (Fig. 8, vertical dashed line). The
pause in activity was specific for the target at the preferred
location in the contralateral field, and the change was significant
(t(74) ⫽ 2.70, p ⬍ 0.009 for two stimuli and t(74) ⫽ 2.76, p ⬍ 0.007
for eight stimuli). As the selection period continued, the neuronal
activity remained below baseline (Fig. 8, rightmost plot). At the
time of the saccade, however, the neuronal activity declined only
for the saccade made to the target at the preferred location.
In summary, the decline in SNr activity around the time a
target is identified and a saccade is made does not occur when the
target is placed symmetrically in the ipsilateral visual field. The
neurons coding the symmetrical nonpreferred target are primarily unaffected by the selection process in this task. The specificity
of the decline also indicates that it is associated with the preferred
field of the neuron rather than with any general arousal effect.
Moreover, a lack of increase when the opposite hemifield target is
identified suggests that there is not a simple, push–pull interaction between the two SNrs.
Figure 8. Comparison of neuronal activity related to identification of a
target in and out of the preferred field of visual-saccade SNr neurons. The
plot shows the mean activity of 38 SNr neurons. The arrangement of this
plot is the same as in Figures 5 and 6. A shows the two possible targets
condition when the target was identified in the preferred field (contra,
thick line) and when the target was identified in the opposite hemifield
(ipsi, thin line). The black bars indicate that there was a statistically
significant difference in the neuronal activity in the two conditions during
the selection interval (100 –500 msec after the target dimmed). B shows
the same traces for the eight possible targets condition. The data are taken
from trials in which the monkeys performed the task correctly. These
neurons show a clear decline in activity associated with the identification
of the target and the initiation of the saccade when they are in the
preferred field and not when in the opposite hemifield. Horizontal calibration: 200 msec.
Adjacent target locations
In the different stimulus configurations, animals also made saccades to targets adjacent to the preferred location and to those in
the hemifield opposite the preferred location. The activity profile
of SNr neurons in the presence of eight possible targets affords a
novel opportunity to examine a recent proposal regarding the role
of the BG in the selection of preferred movements (Mink and
Thatch, 1993; Mink, 1996). According to this scheme, decreases
in activity of BG inhibitory output neurons act to disinhibit
thalamocortical pathways responsible for generating a preferred
movement, and increases act to inhibit thalamocortical pathways
involved in producing the nonselected movement, movements
that would compete with or interfere with the selected movement.
Therefore, we measured the changes in activity of the SNr neurons when each of the eight stimuli in the eight stimulus conditions became the target for the saccade task. Of course this
1890 J. Neurosci., March 1, 2002, 22(5):1883–1894
Basso and Wurtz • Basal Ganglia and Selection
Figure 9. Selectivity indices for SNr visual-saccade neurons and SNr saccade neurons. Neuronal activity is plotted as a function of target direction. The
activity is normalized to the 0° location as the best response of the neurons in the eight possible targets condition. A, B, The visual index shows the activity
of the neurons during the presentation of the visual stimulus 100 –300 msec after onset of the array minus the 200 msec of baseline activity (during fixation
but before the array appeared) divided by the sum of the same two activities. C, D, The selection index was defined as the activity 400 msec after the
target dimmed (beginning at 100 msec after the dim) minus the 400 msec period before the target dimmed divided by the sum of these two activities.
E, F, The initiation index was defined as the 150 msec around the saccade onset (before and after) minus the 200 msec baseline activity divided by the
sum of the same two activities. In each plot, the results for two example neurons are shown (Œ, f) as well as the mean of all neurons (F). Error bars
indicate 1 SEM. The asterisk indicates that the increase was significantly greater than baseline (Mann–Whitney U; p ⬍ 0.014).
analysis was limited to 45° resolution, because this was the minimum angle between the stimuli in our display. Nevertheless, it
allowed us to compare lateral interactions, if any, within the SNr
as we did in the SC and as has been done by Schall and colleagues
(Schall and Hanes, 1993; Schall, 1995; Schall et al., 1995; Schall
and Thompson, 1999) in frontal eye fields.
For both visual-saccade and saccade neurons of the SNr, we
calculated an index, essentially a contrast ratio, at three intervals
of the task: visual, the time around the onset of the visual stimuli;
selection, the time around the dimming of the target; and initiation, the time around saccade onset (Fig. 9). Figure 9 is arranged
so that the preferred response of the neurons in the eight possible
targets condition is rotated to the 0° location.
We calculated the visual selectivity index by dividing the difference of the activity 100 –300 msec after stimulus onset and the
200 msec of baseline activity (during fixation before the array
appeared) by the sum of the activity in the same two intervals (Fig.
9 A, B). A value of 0 indicates no difference in activity from baseline, values below 0 indicate that the activity is less than baseline,
and values ⬎0 indicate that the activity is greater than baseline.
For the visual-saccade neurons, the initial activity was below baseline for the 2 example neurons (Fig. 9A, Œ, f) as well as the sample
of 38 neurons (Fig. 9A, F). This is consistent with the pause in
activity after visual stimulus onset, and also, because this interval
occurred before the target was identified, the activity does not
distinguish between targets or distractors, i.e., they are not tuned.
In contrast, for some saccade neurons, the initial visual activity
increased when eight possible stimuli were presented (Fig. 9B, f,
Œ) but also did not discriminate between targets and distractors.
Although an increase in activity was evident in some neurons and
across the sample initially (Fig. 6), it did not persist for our
measurement interval across the sample (Fig. 9B, F).
The contrast ratio calculated for the selection index was the
difference between the 400 msec before the target was identified
and the 400 msec of activity after the target was identified
(beginning 100 msec after the target dimmed) divided by the sum
of the two activities (Fig. 9C,D). Some visual-saccade neurons
were very broadly tuned during this interval (Fig. 9C, Œ), whereas
others were less broadly tuned and showed a slight increase in
activity only when a target adjacent to the preferred location was
identified (Fig. 9C, f). Indeed, the increase at the 90° location was
significantly different from baseline (Mann–Whitney; *p ⬍ 0.014).
Although opposite in sign, this pattern is reminiscent of that seen
in frontal eye fields (Schall and Hanes, 1993; Schall, 1995; Schall
et al., 1995) and SC (Basso and Wurtz, 1998). Across the sample
of 38 visual-saccade SNr neurons, there was a decline in activity
associated with the preferred target location and less of a decline
for adjacent targets.
Some saccade neurons showed a decline in activity at the time
the target was identified that was broadly tuned for target location
(Fig. 9D, Œ). More commonly, however, saccade neurons showed
only a modest decline in activity at the time the target was
identified (Fig. 9D, F).
The contrast ratio for the initiation index was calculated by
measuring the difference between the 100 msec interval before
and after saccade onset (50 msec before saccade and 50 msec
after saccade) and the baseline activity (200 msec before array
onset during fixation). This difference was then divided by the
sum of the two activities (Fig. 9 E, F ). Visual-saccade neurons of
the SNr were not at all tuned during the initiation period but
exhibited a level of activity that was reduced from baseline (Fig.
9E, F).
For saccade neurons, around the time of saccade initiation, the
neuron that showed broad tuning during the selection period
Basso and Wurtz • Basal Ganglia and Selection
J. Neurosci., March 1, 2002, 22(5):1883–1894 1891
showed a more restricted selectivity (Fig. 9F, Œ). A neuron that
had negligible modulation during the selection period showed a
decline for the preferred saccade location and an enhancement
for all other saccade locations (Fig. 9F, f). Because of the
variability across our sample of saccade neurons, there was very
little obvious tuning during the initiation period (Fig. 9F, F).
In summary, there is a decline in activity for the preferred
target location, with a lesser decline at adjacent target locations.
Interestingly, there is a hint that visual-saccade neurons may
increase their activity for target locations identified adjacent to
the preferred location as if contributing to the suppression of
distracter information. Perhaps this result would be more prominent if our stimuli were placed closer than 45° from one another.
Saccade latency
Because SNr neurons are thought to have a role in the control of
saccade initiation (Hikosaka and Wurtz, 1983d) and the delay
period activity of SC neurons is associated with saccade latency in
certain tasks (Dorris et al., 1997; Basso and Wurtz, 1998), we
compared delay activity and saccade latency. We measured the
300 msec of neuronal activity before the cue to move for all 58
neurons recorded and the saccade latency and calculated the
Pearson r value (Fig. 10). We found significant correlations for 4
of the 58 neurons, 1 of which was in the opposite direction (the
activity decreased as saccade latency increased). In a few cases,
activity preceding saccade generation of SNr neurons was a good
predictor of saccade latency in this task. This is consistent with
findings in SC (Dorris et al., 1997; Basso and Wurtz, 1998). We
also compared saccade latency as a function of the number of
possible saccade targets and found no significant differences. This
probably results from the insertion of a delay (800 –1200 msec)
between the target identification and the onset of the cue to move
that would obscure any latency differences between conditions as
we saw previously (Basso and Wurtz, 1998).
DISCUSSION
We found a series of changes in SNr neuronal activity during the
series of phases of our multitarget selection task. In a set of
neurons that we classified as visual-saccade neurons, there was a
pause in activity after the initial onset of the visual stimulus array
and before the onset of the saccade as has been reported previously (Hikosaka and Wurtz, 1983a). In addition, we found that
the activity after stimulus onset but preceding identification of
the target remained below baseline. When the target was identified, there was a sharp, further decline in activity. This decline in
activity was not just the result of the luminance change of the
target but rather predicted which target the monkey would select
as the goal of a saccade, because the decline was not present when
the monkey made a mistake and made a saccade to a location
other than the one indicated by the cue. The decline for the
preferred target location was accompanied by a lesser decline for
adjacent locations. Of these activity changes, only the pause after
the onset of the array of stimuli was modulated by the number of
possible targets. Most neurons that paused only with saccade
onset showed no modulation related to selecting the visual target.
Contribution of SNr to SC during target selection
Because we used the same behavioral paradigm for the SNr as we
had used previously for the SC (Basso and Wurtz, 1997, 1998), we
can make a detailed comparison between the SNr and SC. In the
SNr neurons that we have studied, the neuronal response during
our multitarget selection task takes the form of a decrease in
Figure 10. Correlation of saccade latency with SNr neuronal activity. A,
Saccade latency as a function of neuronal activity averaged over 300 msec
before the cue to move in a single SNr neuron is plotted. The line is the
regression through the data points. For this neuron, the Pearson r value
was 0.36, which was statistically significant ( p ⬍ 0.05). B, The distribution
of r values calculated for the 58 neurons. Three other SNr neurons had
significant correlations with saccade latency (ⴱ), and the example in A
is indicated (ⴱⴱ). Note that the data are taken from all four possible target conditions, and there are not four “clumps” of data points indicating
that there were no differences in latency between the different target
conditions.
activity, whereas in the SC the change is an increase in activity.
Because the SNr projects to the SC (Hopkins and Niessen, 1976;
Deniau et al., 1978; Graybiel, 1978; Anderson and Yoshida, 1980;
Beckstead, 1983; Hikosaka and Wurtz, 1983d) and is inhibitory
(Chevalier et al., 1981, 1984, 1985; Karabelas and Moschovakis,
1985), we can now consider the extent to which the decrease in
SNr activity contributes to the increase in the SC during target
selection. To facilitate this comparison, we show in Figure 11 the
averaged activity of SC buildup neurons in the multitarget task
that we reported previously (Basso and Wurtz, 1998, their Fig. 4)
along with the averaged activity of the visual-saccade neurons
from SNr (Fig. 5).
Visual activity
The initial visual pause of SNr neurons became less as the
number of possible stimuli increased (Fig. 11 B). This change with
increasing numbers of stimuli could be caused either by the
decreasing certainty that a given stimulus would be the target for
a saccade or by the lateral interactions resulting from the decreasing distances between pools of neurons activated by the stimuli,
or both. In our previous experiments on the SC, we concluded
that the SC visual response was influenced by stimulus interac-
Basso and Wurtz • Basal Ganglia and Selection
1892 J. Neurosci., March 1, 2002, 22(5):1883–1894
have noted, with the addition of a second stimulus, SC activity
changes but SNr activity does not. In addition, the latency of the
visual response in the SNr is slightly longer than in the SC, and so
the modulation of the visual pause seen in the SNr cannot be
responsible for the visual response modulations seen in the SC.
This difference in latency was noted previously (Hikosaka and
Wurtz, 1983a) and is evident by comparing the response profiles
of the two classes of neuron during the array presentation (Fig.
11 A, B, left plots). Therefore, although the SNr could contribute
to the later SC visual response, it clearly cannot be the only input
determining it.
Delay activity
Figure 11. Comparison of SC and SNr neuronal activity in the multitarget task. A, The activity profiles of 40 SC neurons recorded in the
multitarget task. The spike density functions were averaged for each
neuron and superimposed for the four stimulus conditions. Each plot is
aligned as in the other figures. The left plot is aligned on the array onset,
the middle plot is aligned on the target dim, and the right plot is aligned on
saccade initiation. This figure was taken from Basso and Wurtz (1998). B,
The arrangement of this plot is identical to the plot in A except the data
come from SNr recordings (see also Fig. 5). Note that the data from the
SC and the SNr were recorded at different times and from different
monkeys.
tions (Basso and Wurtz, 1998, their Fig. 11) as well as the
certainty of the target location, on the basis of results from
additional experiments. Moreover, it seemed likely that the
change in target location certainty played a prominent role in the
SC, because moving from one stimulus to two was accompanied
by a change in the amplitude of the visual response. This indicated either an effect of the change in certainty or long-range
stimulus interactions, because the second stimulus was always in
the opposite visual field. In the SNr, by contrast, addition of a
second stimulus in the opposite visual field (reducing certainty by
50%) had little effect on the visual response on average. The
reduction became evident only with the addition of more stimuli.
We think this suggests a larger role for close-range stimulus
interactions in the SNr. The relative roles of target certainty and
stimulus interactions will have to be determined in subsequent
experiments.
Regardless of the nature of the visual response in the SNr and
SC, can the change in SNr account for the change in SC? As we
In the preselection period after the response to the visual stimulus onset, the SNr activity remains below the baseline level and
then declines further in the selection period after the target is
identified. These changes are the same regardless of the number
of stimuli. In the SC, the activity in the preselection period
decreases as the number of possible targets increases. When the
target is identified, the SC activity increases to levels seen in the
single target condition regardless of the number of stimuli. Thus
the change of activity at the start of the selection period is the
same in SNr and SC (and of opposite sign), and the activity level
reached in both is independent of the number of possible targets,
that is, of the probability of a stimulus becoming a target. What is
different is that the preselection activity in the SC is higher with
fewer possible targets, whereas in the SNr it is not.
Because the preselection delay period activities were not perfectly matched in the SNr and SC, it is unlikely that SC modulations are a direct result of changes arising from the SNr. Rather,
either the SNr activity seen during this time does not influence
the SC activity or the changes seen in the SNr are indirectly
responsible for changes in SC activity. For example, the reduced
activity during the delay period may exert a permissive disinhibition across the SC map (Basso and Evinger, 1996; Basso et al.,
1996; Schicatano et al., 1997), allowing cortical inputs or intrinsic
SC interactions to directly regulate the level of SC buildup
activity.
In contrast, in the selection period, the SNr could contribute to
the SC activity, but only beyond the initial SC activity change,
because the decline in activity in the SNr had a slightly longer
latency than did the increase in SC, which is similar to the latency
differences in the initial visual response. Examination of the
middle plot of Figure 11 reveals that in the SC, there is initially an
increase and then there appears an additional slight increase. It is
possible that the initial, short-latency increase is caused by the
luminance change in the preferred field that is not evident in SNr
neurons (Fig. 11 A, B, compare middle plots). Thus the decline in
the SNr may be responsible for the longer latency increase in SC
neurons in the selection period after the target is identified.
Furthermore, the decline in the SNr activity at the time of target
selection is clearly related to the saccade that is to be made rather
than just to the target identified, because on error trials when the
target was identified but the monkey did not go to it, the decline
in SNr activity was absent. Unfortunately, there were too few
error trials in the SC experiments to make a quantitative
comparison.
What then is the influence of SNr on SC during target selection? When the target is identified on a given trial, the increase in
the SC could result primarily from the release from inhibition
from the SNr as the activity of the visual-saccade neurons declines. Such a coupling would be consistent with the timing of the
Basso and Wurtz • Basal Ganglia and Selection
inversely related SNr and SC activity. This activity is tied to the
saccade that will be made (at least in the SNr) and therefore is
consistent with the original observations on the close relationship
of the pause of activity in the SNr and the burst of activity in the
SC associated with saccade initiation (Hikosaka and Wurtz,
1983d). We suggest that our observations are most consistent with
the SNr making a substantial contribution to the SC activity as the
target is being selected and as the saccade to that target is being
generated.
Saccade activity
In the SNr visual-saccade neurons, the pause associated with the
saccade was unmodulated with increases in the number of possible targets. Furthermore, across the sample, the SNr saccade
neurons showed no modulation during any period in our task
(Fig. 6). This behavior is consistent with a role for these neurons
exclusively in the initiation of saccadic eye movements (Hikosaka
and Wurtz, 1983c,d; Handel and Glimcher, 1999) and is consistent with our previous findings in the SC saccade-related activity
of both burst and buildup neurons. Importantly, it is consistent
with a substantial contribution of the SNr to the saccadic burst
activity within the SC.
We conclude that in our multitarget selection task, a major,
direct contribution of the SNr to SC activity is at the time of
target selection and subsequently in the generation of the saccade
to the selected target. Although the SNr may play a permissive
role during the time after the stimulus onset and before the target
is indicated, the modulation in SC seen with a different number of
possible stimuli is likely dependent on intrinsic SC mechanisms or
direct input from other sources or both.
SNr spatial interaction and behavioral selection in the
basal ganglia
Our multitarget probability task also provided some information
on the spatial extent of the modulations of SNr activity. A
mechanism based on lateral interactions for saccade target selection has been proposed in frontal eye field (Schall and Hanes,
1993; Schall, 1995; Schall et al., 1995), and a similar mechanism
has been proposed for movement selection in the BG (Mink and
Thatch, 1993; Mink, 1996). This model of BG function emphasizes the role of the BG in the inhibition of unwanted movements
and a selective disinhibition for wanted movements. This model
was developed, in large part, to explain results obtained from
recent anatomical work (Hazrati and Parent, 1992a,b; Parent and
Hazrati, 1993) and reversible inactivation experiments of the
globus pallidus (Mink and Thatch, 1991c).
Our experiments offered the opportunity to study such interactions in the saccadic system that are comparable to those of
Mink and Thach (1993) in the skeletal motor system if we can
regard a saccade to one part of the visual field to be the movement that is facilitated and the saccades to other parts of the field
as those not facilitated. The original experiments of Hikosaka and
Wurtz (1983d) showed that this is the case for the pause in
activity associated with saccadic eye movements made to visual
and remembered targets in one region of the visual field. Our
current experiments show that at the time of target selection, the
most prominent response was a pause for the preferred location
and no change for the rest. Within the SC we had previously
found similar patterns, albeit of opposite sign. In a few SNr
neurons there was an indication that they increased their activity
when stimuli adjacent to the preferred location were identified as
targets (Figs. 9C,F ), and some saccade neurons of the SNr exhib-
J. Neurosci., March 1, 2002, 22(5):1883–1894 1893
ited an increase when many stimuli were present (Fig. 9B). We
take this as providing some evidence for specificity of the lateral
interactions within the BG. In our task, it is important to remember that there was a 45° separation between stimuli, and given the
observation that the SNr did not exhibit remote stimulus effects
(no reduction in pause for two compared with one stimulus) (Fig.
5), the frequency of this finding may depend on the proximity of
distracting stimuli to the target. Indeed, this may increase the
likelihood of observing this phenomenon in SC and frontal eye
field as well. Future experiments are required to map the resolution of these interactive effects.
In conclusion, the multitarget probability task shows that there
is a pause in activity of the SNr neurons with target selection and
saccade initiation to one region of the field, and this pause is
limited to one part of the field. Taken together, these are probably
the best evidence so far within the BG that there is a selective
facilitation (via reduced inhibition) of chosen eye movements
before their execution.
Note added in proof. Identification of the substantia nigra through the
thalamus was described originally by Schultz (1986).
REFERENCES
Anderson ME, Yoshida M (1977) Electrophysiological evidence for
branching nigral projections to the thalamus and the superior colliculus.
Brain Res 137:361–375.
Anderson ME, Yoshida M (1980) Axonal branching patterns and location of nigrothalamic and nigrocollicular neurons in the cat. J Neurophysiol 43:883– 895.
Basso MA, Evinger C (1996) An explanation for reflex blink hyperexcitability in Parkinson’s disease. II. Nucleus raphe magnus. J Neurosci
16:7318 –7330.
Basso MA, Wurtz RH (1997) Modulation of neuronal activity by target
uncertainty. Nature 389:66 – 69.
Basso MA, Wurtz RH (1998) Modulation of neuronal activity in superior colliculus by changes in target probability. J Neurosci
18:7519 –7534.
Basso MA, Powers AS, Evinger C (1996) An explanation for reflex blink
hyperexcitability in Parkinson’s disease. I. Superior colliculus. J Neurosci 16:7308 –7317.
Beckstead RM (1983) Long collateral branches of substantia nigra pars
reticulata axons to thalamus, superior colliculus and reticular formation
in monkey and cat. Multiple retrograde neuronal labeling with fluorescent dyes. Neuroscience 10:767–779.
Boussaoud D, Desimone R, Ungerleider LG (1992) Subcortical connections of visual areas MST and FST in macaques. Vis Neurosci
9:291–302.
Bravo MJ, Nakayama K (1992) The role of attention in different visualsearch tasks. Percept Psychophys 51:465– 472.
Britten KH, Shadlen MN, Newsome WT, Movshon JA (1992) The analysis of visual motion: a comparison of neuronal and psychophysical
performance. J Neurosci 12:4745– 4765.
Chandra R, Optican LM (1997) Detection, classification, and superposition resolution of action potentials in multiunit single-channel recordings by an on-line real-time neural network. IEEE Trans Biomed Eng
44:403– 412.
Chevalier G, Deniau JM, Thierry AM, Feger J (1981) The nigro-tectal
pathway. An electrophysiological reinvestigation in the rat. Brain Res
213:253–263.
Chevalier G, Vacher S, Deniau JM (1984) Inhibitory nigral influence on
tectospinal neurons, a possible implication of basal ganglia in orienting
behavior. Exp Brain Res 53:320 –326.
Chevalier G, Vacher S, Deniau JM, Desban M (1985) Disinhibition as a
basic process in the expression of striatal functions. I. The striato-nigral
influence on tecto-spino/tecto-diencephalic neurons. Brain Res
334:215–226.
Cooper JR, Bloom FE, Roth RH (1986) The biochemical basis of neuropharmacology, Ed 5. Oxford: Oxford University Press.
Crist CF, Yamasaki DSG, Komatsu H, Wurtz RH (1988) A grid system
and a microsyringe for single cell recording. J Neurosci Methods
26:117–122.
Deniau JM, Hammond C, Riszk A, Feger J (1978) Electrophysiological
properties of identified output neurons of the rat substantia nigra (pars
compacta and pars reticulata): evidences for the existence of branched
neurons. Exp Brain Res 32:409 – 422.
Dorris MC, Munoz DP (1998) Saccadic probability influences motor
preparation signals and time to saccadic initiation. J Neurosci
18:7015–7026.
1894 J. Neurosci., March 1, 2002, 22(5):1883–1894
Dorris MC, Paré M, Munoz DP (1997) Neuronal activity in monkey
superior colliculus related to the initiation of saccadic eye movements.
J Neurosci 17:8566 – 8579.
Fuchs AF, Robinson DA (1966) A method for measuring horizontal and
vertical eye movement chronically in the monkey. J Appl Physiol
21:1068 –1070.
Fuller JH, Schlag JD (1976) Determination of antidromic excitation by
the collision test: problems of interpretation. Brain Res 112:283–298.
Glimcher PW, Sparks DL (1992) Movement selection in advance of
action in the superior colliculus. Nature 355:542–545.
Graybiel AM (1978) Organization of the nigrotectal connection: an experimental tracer study in the cat. Brain Res 143:339 –348.
Handel A, Glimcher PW (1999) Quantitative analysis of substantia nigra
pars reticulata activity during a visually guided saccade task. J Neurophysiol 82:3458 –3475.
Handel A, Glimcher PW (2000) Contextual modulation of substantia
nigra pars reticulata neurons. J Neurophysiol 83:3042–3048.
Hays AV, Richmond BJ, Optican LM (1982) A UNIX-based multiple
process system for real-time data acquisition and control. WESCON
Conf Proc 2:1–10.
Hazrati L-N, Parent A (1992a) Convergence of subthalamic and striatal
efferents at pallidal level in primates: an anterograde double-labelling
study with biocytin and PHAL-L. Brain Res 569:336 –340.
Hazrati L-N, Parent A (1992b) The striatopallidal projection displays a
high degree of anatomical specificity in primate. Brain Res
592:213–227.
Hikosaka O, Wurtz RH (1983a) Visual and oculomotor functions of
monkey substantia nigra pars reticulata. I. Relation of visual and
auditory responses to saccades. J Neurophysiol 49:1230 –1253.
Hikosaka O, Wurtz RH (1983b) Visual and oculomotor functions of
monkey substantia nigra pars reticulata. II. Visual responses related to
fixation of gaze. J Neurophysiol 49:1254 –1267.
Hikosaka O, Wurtz RH (1983c) Visual and oculomotor functions of
monkey substantia nigra pars reticulata. III. Memory-contingent visual
and saccade responses. J Neurophysiol 49:1268 –1284.
Hikosaka O, Wurtz RH (1983d) Visual and oculomotor functions of
monkey substantia nigra pars reticulata. IV. Relation of substantia
nigra to superior colliculus. J Neurophysiol 49:1285–1301.
Hopkins DA, Niessen LW (1976) Substantia nigra projections to the
reticular formation, superior colliculus and central gray in the rat, cat,
and monkey. Neurosci Lett 2:253–259.
Judge SJ, Richmond BJ, Chu FC (1980) Implantation of magnetic search
coils for measurement of eye position: an improved method. Vision Res
20:535–538.
Karabelas AB, Moschovakis AK (1985) Nigral inhibitory termination on
efferent neurons of the superior colliculus: an intracellular horseradish
peroxidase study in the cat. J Comp Neurol 239:309 –329.
Lemon R (1984) Methods for neuronal recording in conscious animals.
In: IBRO Handbook Series: methods in the neurosciences, Vol 4, pp
95–102. New York: Wiley.
Basso and Wurtz • Basal Ganglia and Selection
Ma TP (1996) Saccade-related omnivectoral pause neurons in the primate zona incerta. NeuroReport 7:2713–2716.
Mink JW (1996) The basal ganglia: focused selection and inhibition of
competing motor programs. Prog Neurobiol 50:381– 425.
Mink JW, Thatch WT (1991a) Basal ganglia motor control I. Nonexclusive relation of pallidal discharge to five movement modes. J Neurophysiol 65:273–300.
Mink JW, Thatch WT (1991b) Basal ganglia motor control II. Late
pallidal timing relative to movement onset and inconsistent coding of
movement parameters. J Neurophysiol 65:301–329.
Mink JW, Thatch WT (1991c) Basal ganglia motor control III. Pallidal
ablation: normal reaction time, muscle cocontraction, and slow movement. J Neurophysiol 65:330 –351.
Mink JW, Thatch WT (1993) Basal ganglia intrinsic circuits and their
role in behavior. Curr Opin Neurobiol 3:950 –957.
Munoz DP, Wurtz RH (1995) Saccade-related activity in monkey superior colliculus. I. Characteristics of burst and buildup cells. J Neurophysiol 73:2313–2333.
Parent A, Hazrati L-N (1993) Anatomical aspects of information processing in primate basal ganglia. Trends Neurosci 16:111–116.
Parthasarathy HB, Schall JD, Graybiel AM (1992) Distributed but convergent ordering of corticostriatal projections: analysis of frontal eye
field and supplementary eye field in the macaque monkey. J Neurosci
12:4468 – 4488.
Schall JD (1995) Neural basis of saccade target selection. Rev Neurosci
6:63– 85.
Schall JD, Hanes DP (1993) Neural basis of saccade target selection in
frontal eye field during visual search. Nature 366:467– 469.
Schall JD, Thompson KG (1999) Neural selection and control of visually
guided eye movements. Annu Rev Neurosci 22:241–259.
Schall JD, Hanes DP, Thompson KG, King DJ (1995) Saccade target
selection in frontal eye field of macaque. I. Visual and premovement
activation. J Neurosci 15:6905– 6918.
Schicatano EJ, Basso MA, Evinger C (1997) An animal model explains
the origins of cranial dystonia benign essential blepharospasm. J Neurophysiol 77:2842–2846.
Schultz W (1986) Responses of midbrain dopamine neurons to behavioral
trigger stimuli in the monkey. J Neurophysiol 56:1439 –1462.
Selemon LD, Goldman-Rakic PS (1985) Longitudinal topography and
interdigitation of corticostriatal projections in the rhesus monkey.
J Neurosci 5:776 –794.
Selemon LD, Goldman-Rakic PS (1988) Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices
in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior. J Neurosci 8:4049 – 4068.
Thompson KG, Hanes DP, Bichot NP, Schall JD (1996) Perceptual and
motor processing stages identified in the activity of macaque frontal eye
field neurons during visual search. J Neurophysiol 76:4040 – 4054.
Treisman AM, Gelade G (1980) A feature-integration theory of attention. Cognit Psychol 12:97–136.